The goal of this application is to develop SYNPLA, a specific, selective and high-throughput method for marking experience-induced plasticity with single synapse resolution. SYNPLA exploits our understanding of the molecular mechanism of long-term potentiation, which is mediated by the insertion of a specific subtype of glutamate receptor at recently potentiated synapses. In Aim 1 we develop SYNPLA in cultured neurons. In Aims 2 and 3 we apply it to two brain circuits, cortico-amygdalar and cortico-striatal respectively which are known to undergo experience dependent plasticity. SYNPLA has the potential to emerge as a powerful tool for dissecting the circuit mechanisms underlying behavioral plasticity.